Hydrogen Peroxide → HCID 44469439, compound

HRID 881645Notes

Reaction equation

HRID 881645 reaction equation
[C:1]([O:5][C:6](=[O:33])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=3[F:30])[C:16]=2[C:31]#[N:32])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].OO.C(OCC)(=[O:40])C>CS(C)=O>[C:1]([O:5][C:6](=[O:33])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=3[F:30])[C:16]=2[C:31](=[O:40])[NH2:32])[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 44469438HCID 44469438, compound

Product 1

HCID 44469439HCID 44469439, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
63 °C

Procedure

In analogy to GP 5, 386 mg of {3-[2-Cyano-5-fluoro-3-(2-fluoro-4-iodo-phenylamino)-phenoxy]-phenyl}-carbamic acid tert-butyl ester (0.69 mmol, 1 eq) were dissolved in 4.8 ml of DMSO and 0.24 ml of 3 M aq. sodium hydroxide solution (0.72 mmol, 10-80 eq) were added. The mixture was heated to 63° C. and 1.85 ml of hydrogen peroxide solution (aq., 30%) were added over the course of 20 min. The mixture was stirred for another 2 h at 65° C. (bath temp.). The reaction mixture was poured onto 175 ml of ice water. 300 ml of ethyl acetate were added and the phases separated. The aqueous phase was extracted one more time with 150 ml of ethyl acetate. The combined organic layers were washed one time with brine, dried over sodium sulfate, filtered off and concentrated. The concentrate was purified (FlashMaster column chromatography, hexane/ethyl acetate 99/1-60/40) to afford 169 mg (42% yield, 0.29 mmol) of the desired product.

Workup

  1. customthe phases separated
  2. extractionThe aqueous phase was extracted one more time with 150 ml of ethyl acetate
  3. washThe combined organic layers were washed one time with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated
  7. customThe concentrate was purified (FlashMaster column chromatography, hexane/ethyl acetate 99/1-60/40)

Sources & evidence

ORD record
ord-0252002b844c417c9807815a80da2e25
Source dataset
uspto-grants-2015_03
Patent number
US08993630B2

Reaction notes

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